I propose to undertake X-ray structure analyses at atomic resolution on crystals of hagfish insulin and porcine glucagon. The amino acid sequence of hagfish insulin is very different from the sequences of vertebrates such as man and the pig, but the hormone is active in a mammalian system. Preliminary crystallographic and sequence studies suggest that the general structure of the hagfish insulin molecule is similar to that found in porcine insulin, while the association properties are different. Hagfish insulin forms an exact dimer in tetragonal crystals with one insulin molecule in the asymmetric unit, and does not form a hexamer. I plan to compare the structure of the hagfish hormone with that of the pig in order to correlate sequence, structure and activity. Glucagon affects several of the metabolic processes responsive to insulin, and the two hormones are often antagonists. Commercial glucagon contains a number of impurities, and I propose to use purified glucagon to prepare native and zinc glucagon crystals for X-ray structure analysis. The structural information will then be used to interpret biochemical function.